Phase I/II Study of Intravenous Infusion of Tetra-o-Methyl Nordihydroguaiaretic Acid (EM-1421) in Subjects With Recurrent High Grade Glioma
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
Phase I/II Study of Intravenous Infusion of Tetra-o-Methyl Nordihydroguaiaretic Acid (EM-1421) in Subjects With Recurrent High Grade Glioma
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) of tetra-O-methyl nordihydroguaiaretic acid
(EM-1421) in patients with recurrent high-grade glioma. (Phase I)
- Determine the response rate in patients treated with EM-1421 administered at the MTD.
(Phase II)
Secondary
- Describe the pharmacokinetics of EM-1421 in these patients. (Phase I)
- Determine the effects of hepatic enzyme-inducing anticonvulsants on the pharmacokinetic
profile of EM-1421 in these patients. (Phase I)
- Determine the toxicity of this drug in these patients. (Phase I)
- Assess the tolerability of this drug in these patients. (Phase I)
- Assess the antitumor activity of this drug, in terms of overall survival. (Phase I)
- Assess the overall survival of these patients. (Phase II)
- Assess the safety and tolerability of EM-1421 given at the MTD in these patients.
(Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II,
open-label study. Patients are stratified according to the use of cytochrome P450-inducing
anticonvulsants (use of anticonvulsant drugs that induce hepatic metabolic enzymes vs use of
anticonvulsant drugs that cause modest or no induction of hepatic metabolic enzymes or no
use of anticonvulsant drugs).
- Phase I: Patients receive tetra-O-methyl nordihydroguaiaretic acid (EM-1421) IV on days
1-5. Treatment repeats every 28 days in the absence of disease progression or
unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of EM-1421 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6
patients experience dose-limiting toxicity.
- Phase II: Patients receive EM-1421 as in phase I at the MTD. Blood is collected on days
1 and 5 of courses 1 and 2 of treatment for pharmacokinetic studies.
After completion of study therapy, patients are followed every 2 months.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed malignant glioma, including any of the following subtypes:
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Glioblastoma multiforme
- Progressive or recurrent disease after radiation therapy with or without chemotherapy
- Patients with a previous low-grade glioma that has progressed to
biopsy-confirmed high-grade glioma after radiation therapy with or without
chemotherapy are eligible
- Contrast-enhancing measurable disease by MRI or CT scan
PATIENT CHARACTERISTICS:
- Karnofsky performance status 60-100%
- Absolute neutrophil count ≥ 1,500/mm³
- Hemoglobin ≥ 9 g/dL
- Platelet count ≥ 100,000/mm³
- Creatinine ≤ 1.5 mg/dL
- Bilirubin ≤ 1.5 mg/dL
- Transaminases ≤ 4 times upper limit of normal
- PT/PTT/INR normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for 2 months
after completion of study treatment
- Mini Mental State Exam score ≥ 15
- No serious concurrent infection or medical illness that would impair the ability to
safely receive study treatment
- No other prior or concurrent malignancy within the past 5 years except for curatively
treated carcinoma in situ or basal cell carcinoma of the skin
- No known sensitivity to any of the study medication components (i.e., polyethylene
glycol [PEG 300] and 2-hydroxypropyl β-cyclodextrin)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from prior therapy
- At least 3 months since prior radiation therapy
- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- At least 2 weeks since prior Federal Drug Administration (FDA)-approved noncytotoxic
therapy (e.g., celecoxib or thalidomide)
- At least 3 weeks since prior investigational noncytotoxic agents
- At least 10 days since prior anticonvulsant drugs that induce hepatic metabolic
enzymes, including any of the following:
- Phenytoin
- Carbamazepine
- Phenobarbital
- Primidone
- Oxcarbazepine
- Ethosuximide
- No other concurrent therapy for this tumor, including systemic chemotherapy or
radiation therapy
- Concurrent steroids allowed
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose (Phase I)
Safety Issue:
Yes
Principal Investigator
Stuart A. Grossman, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
NABTT-0503 CDR0000515952
NCT ID:
NCT00404248
Start Date:
January 2007
Completion Date:
February 2012
Related Keywords:
- Brain and Central Nervous System Tumors
- adult anaplastic astrocytoma
- adult anaplastic oligodendroglioma
- adult giant cell glioblastoma
- recurrent adult brain tumor
- adult glioblastoma
- adult gliosarcoma
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia, Pennsylvania 19104-4283 |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
| Cleveland Clinic Taussig Cancer Center | Cleveland, Ohio 44195 |
| Josephine Ford Cancer Center at Henry Ford Hospital | Detroit, Michigan 48202 |
| Winship Cancer Institute of Emory University | Atlanta, Georgia 30322 |
| Wake Forest University Comprehensive Cancer Center | Winston-Salem, North Carolina 27157-1096 |
| Massachusetts General Hospital | Boston, Massachusetts 02114-2617 |
| H. Lee Moffitt Cancer Center and Research Institute at University of South Florida | Tampa, Florida 33612 |
| UAB Comprehensive Cancer Center | Birmingham, Alabama 35294 |
